In the middle of the night of May 22, the international authoritative medical journal "The Lancet" published online the results of the world's first human clinical trial of COVID-19 vaccine, showing that the adenovirus vector vaccine from Academician Chen Wei is safe and can produce COVID- 19 The double immune response of the virus.
"The Lancet" editor-in-chief Richard Horton shared the news via social media, and praised: The first human experiment results of this COVID-19 vaccine found that it has good safety and tolerance, and Can induce a rapid immune response. "These results represent an important milestone." The main results of the
paper are as follows: After
volunteers were vaccinated with this vaccine, enzyme-linked antibodies and neutralizing antibodies began to increase significantly from the 14th day of vaccination, and at the 28th day after vaccination. Peak day. The specific T cell response peaked on the 14th day after inoculation.
Among all the 108 volunteers tested, 30 volunteers in the low-dose and middle-dose groups and 27 in the high-dose group respectively reported adverse events within 7 days after vaccination. The most common ones are fever, fatigue, headache and muscle pain. Among all reports, most were mild or moderate, and no serious adverse events were reported within 28 days after vaccination. Academician
Chen Wei said that these test results are an important milestone. These test results show that a single dose of the adenovirus vector vaccine can produce virus-specific antibodies and T cells within 14 days, making the vaccine have the potential to be further studied.
However, Academician Chen also said that these test results should be interpreted with caution. The challenge of developing a COVD-19 vaccine is unprecedented, and the ability to trigger the aforementioned immune response does not necessarily mean that the vaccine can protect people from COVID-19. Dr.
Tao commented:
1 Unreserved disclosure of data
This paper published the safety and immune effect evidence of all 108 Phase I volunteers. In contrast, Modena disclosed 1/3 of the data on the website. The rigor is higher than the latter.
2 The vaccine is safe. Although
has seen that 2/3 of the volunteers have reported adverse events, due to the lack of a placebo control group, it is actually impossible to judge whether these adverse events are caused by the vaccine. These post-vaccination health problems are only preventive adverse events (AEFI, Adverse Event Following Immunization), rather than clearly causal adverse reactions (AD, Adverse Reaction).
According to Dr. Tao’s experience, the AD that is really attributable to the vaccine in these AEFIs may only account for 10% to 30%. A phase II clinical trial with a control group can verify or beat Dr. Tao's speculation.
3 The first report of important cellular immunity
The previous COVID-19 vaccine information disclosure usually only talks about antibodies, but in fact, antibodies are only one of the two major mechanisms of human immunity to microorganisms, which are usually called humoral immunity. Another major mechanism is cellular immunity, which can eliminate virus-infected cells. If these two mechanisms are compared to weapons, then the humoral immune antibody is equivalent to a machine gun, which kills directly and highly; cellular immunity is equivalent to heavy artillery, which can destroy the city (cell) occupied by the virus. The
study on people infected with SARS, MERS and COVID-19 found that the increase in virus-specific antibodies is temporary and declines rapidly after the patient recovers, while specific T cell responses play a crucial role in immunity effect.
has reason to believe that if the vaccine can cause humoral immunity and cellular immunity at the same time, then it is more likely to succeed. Vector vaccines, mRNA vaccines and DNA vaccines are considered to cause cellular immunity at the same time (this is an advantage), so the results of cellular immunity will be observed, while inactivated vaccines usually cannot cause cellular immunity, so cellular immunity observations are generally not done during research.
4 It is not yet possible to determine the effective antibody and cellular immunity standards
Since the Phase I human clinical trial mainly observes safety and there is no control group, it is impossible to determine the effective antibody level and cellular immunity level of protection.
From the results of this study, the enzyme-linked antibody against the RBD region of the virus S protein has a 4-fold growth rate of about 50% 14 days after vaccination, 28 daysReach more than 95%.
is more important, and the 4-fold growth rate of neutralizing antibodies that directly fixes the virus is about 30% at 14 days and about 60% at 28 days. Dr. Tao thinks this result is not ideal, if it can be above 90%, it would be fine. However, since the effective antibody standard has not been determined, and cellular immunity is equally important, the result of the 4-fold growth rate of neutralizing antibody is not so attractive yet does not explain the problem.
5 disclosed the optimistic results of animal experiments.
mentioned the performance of the vaccine in animal experiments in the discussion section of the article: 7 of the 8 ferrets vaccinated withstood the virus attack and the virus could not be detected; those who were not vaccinated Only one of the eight control ferrets could not detect the virus. Dr.
Tao hopes that the results of this animal experiment will be published as soon as possible.
6 Human background adenovirus antibodies will affect the vaccine effect.
adenovirus itself is a common virus that causes the common cold. Many people have certain adenovirus antibodies in their bodies, which may affect the performance of adenovirus vector vaccines. The
study showed that before vaccination, 44% to 56% of the low, medium and high dose groups had high levels of background adenovirus antibodies (titer ≥ 1:200); their adenovirus antibodies increased by 4 times after vaccination The rates are 25%, 37%, and 63%, respectively, which are positively correlated with vaccine dose. The multivariate analysis of
shows that if there is a high level of adenovirus antibodies before vaccination, the COVID-19 virus neutralizing antibodies of the vaccine will be reduced, regardless of the dose of the vaccine. The older the age, the lower the level of COVID-19 virus neutralizing antibodies.
In other words, people who often catch colds and those who are older will have a weaker immune response to this vaccine. However, whether this weaker immune response substantially affects the protective effect of the vaccine remains uncertain. If this effect is confirmed in the future, it can be solved by adjusting the vaccine dose or increasing the number of inoculations.
Summary
This is the world's first officially published human clinical trial result of COVID-19 vaccine and the world's first show of adenovirus vector COVID-19 vaccine. The results are quite optimistic.
The previous discussion on the effect of the COVID-19 vaccine focused on antibodies (humoral immunity), which may have caused the public to misunderstand that the vaccine effect is only reflected in antibodies. This study mentioned the importance of cellular immunity, and then discussing the performance of vaccines, we should consider both antibodies and cellular immunity.
